Receptor-Mediated Changes in Hepatocyte Phosphoinositide Metabolism
Hepatocytes respond to a variety of extracellular stimuli which evoke intracellular metabolic changes. Among these, glucagon, isoproterenol, and other β-adrenergic receptor agonists act via elevation of cAMP levels, which leads to activation of glycogen phosphorylase and a resultant onset of glycogenolysis. However, another group of stimuli, which includes α1 adrenergic agonists, vasopressin, and angiotensin II, each acting at a distinct cell surface receptor, enhances glycogen phosphorylase activity in rat hepatocytes. The mechanism is cAMP independent and involves a rapid rise in free cytosolic Ca2+ [6,10,31]. The mechanism of Ca2+ mobilization is unsettled, but cumulative evidence suggests that the ion is released from at least one and possible several intracellular sites. An increase in cytosolic Ca2+ may also constitute a step in the initiation of other cellular events such as inactivation of glycogen synthetase and stimulation of potassium fluxes across the plasma membrane . The release of Ca2+ into the cytosol appears to be followed by extensive net uptake of the ion from the external medium, perhaps to replenish depleted intracellular stores.
KeywordsNorepinephrine Cytosol Epinephrine Glucagon Vasopressin
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